The Duke University Adult ACTU has contributed to the ACTG scientific agenda over the past three years. The most notable contributions from Duke include the introduction of two pathogenesis-based ACTU protocols (380 and A5049), and the integration of Duke investigators into the scientific leadership as the Chairs of five ACTG trials and as members of numerous ACTG scientific committees. Duke University contributions to the AACTG are facilitated by the clinical and basic science expertise in HIV infection at the Medical Center, and environment of collaboration in translational research. A Scientific Advisory Committee composed of basic and clinical scientists assists the Duke ACTU site investigators in the development of potential ACTG studies. The Duke University Adult ACTU has steadily increased its enrollment into ACTG studies, especially labor intensive scientifically rigorous trials, and studies enrolling treatment-naive subjects. In 1998, the unit enrolled 72 subjects into main ACTG studies and 44 subjects into ACTG substudies. As a result of these efforts and efficiency at the site, Duke ranked fourth among the 30 existing ACTUs in the lowest median cost per weighted accrual during 1997- 1998. The Duke ACTU also had the lowest loss to follow-up rate in the ACTG. The applicant proposes to make substantial contributions to longitudinal research such as the Longitudinal Linked Randomized Trial (ALLRT) protocol. Subjects enrolled through the Duke University Adult ACTU reflect the demographics of HIV infection in North Carolina. The recruitment of historically underrepresented persons is assisted by the efforts of the Community Advisory Board (CAB) and Outreach Core, the provision of comprehensive on-site primary care, the Women s Clinic, and a NIDA supplement to the ACTU which supports on-site substance abuse counseling. During the next five years, the Duke University Adult ACTU proposes to emphasize investigations into the cellular reservoir of HIV, immunologic recovery during antiretroviral therapy, the enhancement of HIV-specific immune responses, and the development of improved antiretroviral treatment strategies such as treatment intensification. The Duke ACTU also proposes to continue to enter 75 new patients into main ACTG studies and 20 new patients into ACTG substudies annually. Given the continuing referrals of newly diagnosed persons with HIV infection to Duke, the Duke University Adult ACTU plans to provide the opportunity for recruitment of these persons into ACTG studies of treatment initiation. The applicants anticipate that Duke will continue as an efficient, cost-effective ACTU that contributes to the ACTG scientific agenda.